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Sponsors and Collaborators: |
Children's Oncology Group National Cancer Institute (NCI) |
Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00408005 |
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia.
PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia.
Condition | Intervention | Phase |
Leukemia |
Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: nelarabine Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate Procedure: radiation therapy |
Phase III |
MedlinePlus related topics: | Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Active Control |
Official Title: | Intensified Methotrexate, Nelarabine (Compound 506U78; IND #52611) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia |
Estimated Enrollment: | 1380 |
Study Start Date: | January 2007 |
Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
Consolidation arm I (weeks 6-13): Active Comparator
Patients receive methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43 and 50; and pegaspargase intramuscularly (IM) on days 15 and 43. Patients with Down syndrome (DS) also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic cranial radiotherapy (CRT) (1,200 cGy/dose) once daily on days 15-19 and 22-24. Patients with low-risk disease do not undergo CRT.
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Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: leucovorin calcium
Given orally or IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Consolidation arm II (weeks 6-13): Active Comparator
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; MTX IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV or SC on days 8-11, 15-18, 50-53 and 57-60; oral mercaptopurine on days 8-21 and 50-63; vincristine IV on days 22, 29, 64, and 71; and pegaspargase IM on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT once daily on days 22-26 and 29-31.
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Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Consolidation arm III (weeks 6-13): Active Comparator
Patients receive MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm I. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm I.
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Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Consolidation arm IV (weeks 6-13): Active Comparator
Patients receive nelarabine, MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm II. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm II.
|
Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Interim maintenance arm I (weeks 14-21): Active Comparator
Patients receive vincristine IV and escalating doses of MTX IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 31. Patients with DS also receive oral leucovorin calcium 48 and 60 hours after each MTX IT dose.
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Drug: leucovorin calcium
Given orally or IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
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Interim maintenance arm II (weeks 17-24): Active Comparator
Patients receive vincristine, escalating doses of MTX, pegaspargase, and MTX IT as in arm I.
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Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: vincristine sulfate
Given IV
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Interim maintenance arm III (weeks 14-21): Active Comparator
Patients receive high-dose methotrexate (HDMTX) IV over 24 hours and vincristine IV on days 1, 15, 29, and 43; oral mercaptopurine on days 1-56; and MTX IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or orally once every 6 hours for 3 doses.
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Drug: leucovorin calcium
Given orally or IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
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Interim maintenance arm IV (weeks 17-24): Active Comparator
Patients receive HDMTX, vincristine, mercaptopurine, MTX IT, and leucovorin calcium as in arm III.
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Drug: leucovorin calcium
Given orally or IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
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Delayed intensification arm I (weeks 22-30): Active Comparator
Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients ≥ 10 years of age and for patients with DS); doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6, AND day 43; MTX IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; and oral thioguanine on days 29-42. Patients with DS also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose.
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Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: dexamethasone
Given orally and IV
Drug: doxorubicin hydrochloride
Given IV
Drug: leucovorin calcium
Given orally or IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: thioguanine
Given orally
Drug: vincristine sulfate
Given IV
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Delayed intensification arm II (weeks 25-33): Active Comparator
Patients receive vincristine IV on days 1, 8, 15, and 50; dexamethasone IV or orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients ≥ 10 years of age); doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6 AND day 50; MTX IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV or SC on days 36-39 and 43-46; and oral thioguanine on days 36-49.
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Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: dexamethasone
Given orally and IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: thioguanine
Given orally
Drug: vincristine sulfate
Given IV
|
Delayed intensification arm III (weeks 22-30): Active Comparator
Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, cyclophosphamide, cytarabine, and thioguanine as in arm I. Patients with intermediate- or high-risk disease (CNS1 or CNS2 disease) undergo prophylactic CRT (1,200 cGy/dose) once daily on days 50-54 and 57-59.
|
Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: dexamethasone
Given orally and IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: thioguanine
Given orally
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Delayed intensification arm IV (weeks 25-33): Active Comparator
Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, nelarabine, cyclophosphamide, cytarabine, and thioguanine as in arm II. Patients with intermediate- or high-risk disease (CNS 1 or CNS2 disease) undergo prophylactic CRT on days 50-54 and 57-59.
|
Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV or subcutaneously
Drug: dexamethasone
Given orally and IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: pegaspargase
Given intramuscularly
Drug: thioguanine
Given orally
Drug: vincristine sulfate
Given IV
Procedure: radiation therapy
Some patients undergo testicular and/or prophylactic cranial radiotherapy.
|
Maintenance arm I (week 31 until the end of therapy): Active Comparator
Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).
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Drug: dexamethasone
Given orally and IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
|
Maintenance arm II (weeks 34-69): Active Comparator
Patients receive vincristine IV on days 1 and 57; oral dexamethasone on days 1-5 and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; MTX IT on day 1; and nelarabine IV over 60 minutes on days 29-33. Treatment (that includes nelarabine) repeats every 84 days for 3 courses. Patients then receive treatment (without nelarabine) as follows: vincristine IV on days 1 and 57; oral dexamethasone on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).
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Drug: dexamethasone
Given orally and IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: vincristine sulfate
Given IV
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Maintenance arm III (week 31 until the end of therapy): Active Comparator
Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX IT as in arm I. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).
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Drug: dexamethasone
Given orally and IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
|
Maintenance arm IV (weeks 34-69): Active Comparator
Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, MTX IT, and nelarabine as in arm II. Patients then receive treatment (without nelarabine) as follows: vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).
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Drug: dexamethasone
Given orally and IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV
Drug: nelarabine
Given IV
Drug: vincristine sulfate
Given IV
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Show Detailed Description |
Ages Eligible for Study: | 1 Year to 30 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Newly diagnosed T-cell acute lymphoblastic leukemia, meeting the following criteria:
Leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (CD19/CD22/CD20) AND express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Show 57 Study Locations |
Children's Oncology Group |
National Cancer Institute (NCI) |
Study Chair: | Stuart S. Winter, MD | University of New Mexico |
Investigator: | Kimberly Dunsmore, MD | University of Virginia |
Clinical trial summary from the National Cancer Institute's PDQ® database 
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Study ID Numbers: | CDR0000514500, COG-AALL0434 |
First Received: | December 4, 2006 |
Last Updated: | October 21, 2008 |
ClinicalTrials.gov Identifier: | NCT00408005 |
Health Authority: | Unspecified |
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